14,207 research outputs found

    Computer aids for worst case electronic circuit design

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    Computer aids for worst case electronic circuit desig

    An evolutionary perspective on the kinome of malaria parasites

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    Malaria parasites belong to an ancient lineage that diverged very early from the main branch of eukaryotes. The approximately 90-member plasmodial kinome includes a majority of eukaryotic protein kinases that clearly cluster within the AGC, CMGC, TKL, CaMK and CK1 groups found in yeast, plants and mammals, testifying to the ancient ancestry of these families. However, several hundred millions years of independent evolution, and the specific pressures brought about by first a photosynthetic and then a parasitic lifestyle, led to the emergence of unique features in the plasmodial kinome. These include taxon-restricted kinase families, and unique peculiarities of individual enzymes even when they have homologues in other eukaryotes. Here, we merge essential aspects of all three malaria-related communications that were presented at the Evolution of Protein Phosphorylation meeting, and propose an integrated discussion of the specific features of the parasite's kinome and phosphoproteome

    The future of biomolecular simulation in the pharmaceutical industry: what we can learn from aerodynamics modelling and weather prediction. Part 1. understanding the physical and computational complexity of in silico drug design

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    The predictive power of simulation has become embedded in the infrastructure of modern economies. Computer-aided design is ubiquitous throughout industry. In aeronautical engineering, built infrastructure and materials manufacturing, simulations are routinely used to compute the performance of potential designs before construction. The ability to predict the behaviour of products is a driver of innovation by reducing the cost barrier to new designs, but also because radically novel ideas can be piloted with relatively little risk. Accurate weather forecasting is essential to guide domestic and military flight paths, and therefore the underpinning simulations are critical enough to have implications for national security. However, in the pharmaceutical and biotechnological industries, the application of computer simulations remains limited by the capabilities of the technology with respect to the complexity of molecular biology and human physiology. Over the last 30 years, molecular-modelling tools have gradually gained a degree of acceptance in the pharmaceutical industry. Drug discovery has begun to benefit from physics-based simulations. While such simulations have great potential for improved molecular design, much scepticism remains about their value. The motivations for such reservations in industry and areas where simulations show promise for efficiency gains in preclinical research are discussed. In this, the first of two complementary papers, the scientific and technical progress that needs to be made to improve the predictive power of biomolecular simulations, and how this might be achieved, is firstly discussed (Part 1). In Part 2, the status of computer simulations in pharma is contrasted with aerodynamics modelling and weather forecasting, and comments are made on the cultural changes needed for equivalent computational technologies to become integrated into life-science industries

    Assessing the Risk of Disc Heniation Related to Landing Impact Following Long-duration Spacecraft

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    Previous research has shown that crewmembers returning on the Space Shuttle have an increased incidence of herniated nucleus pulposus after spaceflight. This increased risk is thought to be related to disc volume expansion due to unloading and prolonged exposure to microgravity. Although there is an increased risk of disc herniation in Space Shuttle astronauts, it is unknown if dynamic landing loads further contribute to the risk of herniation. To determine if dynamic loads increase the risk of incidence, data from crewmembers (excluding cosmonauts) returning on the Soyuz spacecraft will be compared to Space Shuttle astronauts. These data will be obtained from the Lifetime Surveillance of Astronaut Health (LSAH) Project at NASA. Severity and incidence after spaceflight will be mined from the data, and statistical analyses will be used to determine if Soyuz crewmembers have a higher incidence of disc herniation than Space Shuttle crewmembers. The results are expected to show no difference between Space Shuttle and Soyuz crewmembers, indicating that higher dynamic loads on landing and long-duration spaceflight do not significantly increase the risk of disc herniation. If no difference is shown between the two crewmember populations, then disc volume expansion due to microgravity does not significantly increase the risk of injury due to dynamic loads for deconditioned crewmembers. Any risk associated with deconditioning would be primarily due to bone structure changes and resulting bone strength changes. This study is an important first step in determining whether the spinal disc plays a role in injury due to dynamic loads

    Data Mining of Historical Human Data to Assess the Risk of Injury due to Dynamic Loads

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    The NASA Occupant Protection Group is charged with ensuring crewmembers are protected during all dynamic phases of spaceflight. Previous work with outside experts has led to the development of a definition of acceptable risk (DAR) for space capsule vehicles. The DAR defines allowable probability rates for various categories of injuries. An important question is how to validate these probabilities for a given vehicle. One approach is to impact test human volunteers under projected nominal landing loads. The main drawback is the large number of subject tests required to attain a reasonable level of confidence that the injury probability rates would meet those outlined in the DAR. An alternative is to mine existing databases containing human responses to impact. Testing an anthropomorphic test device (ATD) at the same humanexposure levels could yield a range of ATD responses that would meet DAR. As one aspect of future vehicle validation, the ATD could be tested in the vehicle's seat and suit configuration at nominal landing loads and compared with the ATD responses supported by the human data set. This approach could reduce the number of humanvolunteer tests NASA would need to conduct to validate that a vehicle meets occupant protection standards. METHODS: The U.S. Air Force has recorded hundreds of human responses to frontal, lateral, and spinal impacts at many acceleration levels and pulse durations. All of this data are stored on the Collaborative Biomechanics Data Network (CBDN), which is maintained by the Wright Patterson Air Force Base (WPAFB). The test device for human occupant restraint (THOR) ATD was impact tested on WPAFB's horizontal impulse accelerator (HIA) matching humanvolunteer exposures on the HIA to 5 frontal and 3 spinal loading conditions. No human injuries occurred as a result of these impact conditions. Peak THOR response variables for neck axial tension and compression, and thoracicspine axial compression were collected. Maximal chest deflection was determined from motion capture video of the impact test. HIC 15 and BRIC were calculated from head acceleration responses. Given the number of human subjects for each test condition a confidence interval of injury probability will be obtained. RESULTS: Results will be discussed in terms of injuryrisk probability estimates based on the human data set evaluated. Also, gaps in the data set will be identified. These gaps could be one of two types. One is areas where additional THOR testing would increase the comparable human data set, thereby improving confidence in the injury probability rate. The other is where additional human testing would assist in obtaining information on other acceleration levels or directions. DISCUSSION: The historical human data showed validity of the THOR ATD for supplemental testing. The historical human data are limited in scope, however. Further data are needed to characterize the effects of sex, age, anthropometry, and deconditioning due to spaceflight on risk of injur

    Spontaneous emission of an atomic dipole near a semi-transparent mirror in free space

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    Atom-field interactions near optical interfaces have a wide range of applications in quantum technology. Motivated by this, this paper revisits the spontaneous emission of atomic dipoles in the presence of a two sided semi-transparent mirror. First we review the main properties of the quantised electromagnetic field near a semitransparent mirror. To do so, we employ a quantum mirror image detector method which maps the experimental setup which we consider here onto analogous free space scenarios. We emphasise that the local density of states of the electromagnetic field depends on the reflection rates of both sides of the mirror surface. Hence it is not surprising that also the spontaneous decay rate of an atomic dipole in front of a semi-transparent mirror depends on both reflectance rates. Although the effect which we describe here only holds for relatively short atom-mirror distances, it can aid the design of novel photonics devices

    Staging superstructures in high-TcT_c Sr/O co-doped La2x_{2-x}Srx_xCuO4+y_{4+y}

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    We present high energy X-ray diffraction studies on the structural phases of an optimal high-TcT_c superconductor La2x_{2-x}Srx_xCuO4+y_{4+y} tailored by co-hole-doping. This is specifically done by varying the content of two very different chemical species, Sr and O, respectively, in order to study the influence of each. A superstructure known as staging is observed in all samples, with the staging number nn increasing for higher Sr dopings xx. We find that the staging phases emerge abruptly with temperature, and can be described as a second order phase transition with transition temperatures slightly depending on the Sr doping. The Sr appears to correlate the interstitial oxygen in a way that stabilises the reproducibility of the staging phase both in terms of staging period and volume fraction in a specific sample. The structural details as investigated in this letter appear to have no direct bearing on the electronic phase separation previously observed in the same samples. This provides new evidence that the electronic phase separation is determined by the overall hole concentration rather than specific Sr/O content and concommittant structural details.Comment: 8 pages, incl. 4 figure
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